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- Title
CD4<sup>+</sup> CD25<sup>+</sup> transforming growth factor-β-producing T cells are present in the lung in murine tuberculosis and may regulate the host inflammatory response.
- Authors
Mason, C. M.; Porretta, E.; Zhang, P.; Nelson, S.
- Abstract
CD4+ CD25+ regulatory T cells produce the anti-inflammatory cytokines transforming growth factor (TGF)-β or interleukin (IL)-10. Regulatory T cells have been recognized to suppress autoimmunity and promote self-tolerance. These cells may also facilitate pathogen persistence by down-regulating the host defence response during infection with Mycobacterium tuberculosis. We evaluated TGF-β+ and IL-10+ lung CD4+ CD25+ T cells in a murine model of M. tuberculosis. BALB/c mice were infected with ∼50 colony-forming units of M. tuberculosis H37Rv intratracheally. At serial times post-infection, lung cells were analysed for surface marker expression (CD3, CD4, CD25) and intracellular IL-10, TGF-β, and interferon (IFN)-γ production (following stimulation in vitro with anti-CD3 and anti-CD28 antibodies). CD4+ lung lymphocytes were also selected positively after lung digestion, and stimulated in vitro for 48 h with anti-CD3 and anti-CD28 antibodies in the absence and presence of anti-TGF-β antibody, anti-IL-10 antibody or rmTGF-β soluble receptor II/human Fc chimera (TGFβsrII). Supernatants were assayed for elicited IFN-γ and IL-2. Fluorescence activated cell sorter analyses showed that TGF-β- and IL-10-producing CD4+ CD25+ T cells are present in the lungs of infected mice. Neutralization of TGF-β and IL-10 each resulted in increases in elicited IFN-γ, with the greatest effect seen when TGFβsrII was used. Elicited IL-2 was not affected significantly by TGF-β neutralization. These results confirm the presence of CD4+ CD25+ TGF-β+ T cells in murine pulmonary tuberculosis, and support the possibility that TGF-β may contribute to down-regulation of the host response.
- Publication
Clinical & Experimental Immunology, 2007, Vol 148, Issue 3, p537
- ISSN
0009-9104
- Publication type
Academic Journal
- DOI
10.1111/j.1365-2249.2007.03371.x